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首页> 外文期刊>Journal of psychopharmacology >Inhibition of N-methyl-D-aspartate receptor function appears to be one of the common actions for antidepressants.
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Inhibition of N-methyl-D-aspartate receptor function appears to be one of the common actions for antidepressants.

机译:N-甲基-D-天冬氨酸受体功能的抑制似乎是抗抑郁药的常见作用之一。

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摘要

In order to explore the possible common action mechanisms of three kinds of classical antidepressants, inhibition of drugs on the N-methyl-D-aspartate (NMDA)-Ca(2)-nitric oxide synthase (NOS) signal pathway was observed. With 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and lactic dehydrogenase (LDH) assay, classical antidepressants, desipramine (1, 10 microM), fluoxetine (0.625-10 microM) or moclobemide (2.5, 10 microM) antagonized NMDA 300 M induced-lesion in PC12 cells. Using fura-2/AM (acetoxymethyl ester) labelling assay, desipramine or fluoxetine at doses 1, 5 microM attenuated the intracellular Ca(2) overload induced by NMDA 200 microM for 24 h in PC12 cells. Meanwhile, using confocal microscope, it was also found that desipramine 5 microM, fluoxetine 2.5 microM or moclobemide 10 microM decreased the NMDA 20 microM induced intracellular Ca(2) overload in primarily cultured rat hippocampal neurons. Furthermore, desipramine (1, 5 microM), fluoxetine (1, 5 microM) or moclobemide (2.5, 10 microM) significantly inhibited NOS activity in NMDA (300 microM) treated PC12 cells for 4h. In summary, we suggest that inhibition on the function of NMDA-Ca(2) -NOS signal pathway appears to be one of the common actions for antidepressants despite their remarkably different structures, which is expected to have great implication for the evaluation and screening in vitro of new antidepressants.
机译:为了探讨三种经典抗抑郁药的可能的共同作用机制,观察到药物对N-甲基-D-天冬氨酸(NMDA)-Ca(2)-一氧化氮合酶(NOS)信号通路的抑制作用。采用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑(MTT)测定法和乳酸脱氢酶(LDH)测定法,经典抗抑郁药,地昔帕明(1,10 microM),氟西汀(0.625-10 microM)或吗氯贝胺(2.5,10 microM)拮抗NMDA 300 M诱导PC12细胞损伤。使用呋喃2 / AM(乙酰氧基甲酯)标记测定,剂量1,5 microM的地昔帕明或氟西汀减弱了PC12细胞中NMDA 200 microM诱导24 h的细胞内Ca(2)超负荷。同时,使用共聚焦显微镜,还发现在主要培养的大鼠海马神经元中,desipramine 5 microM,fluoxetine 2.5 microM或moclobemide 10 microM降低了NMDA 20 microM诱导的细胞内Ca(2)超负荷。此外,地昔帕明(1,5 microM),氟西汀(1,5 microM)或莫洛贝米(2.5,10 microM)在NMDA(300 microM)处理的PC12细胞中显着抑制NOS活性达4小时。总而言之,我们建议抑制NMDA-Ca(2)-NOS信号通路的功能似乎是抗抑郁药的常见作用之一,尽管它们的结构明显不同,这有望对评估和筛选具有重要意义。新型抗抑郁药的体外试验。

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